Evaluation of screening for myocardial ischaemia in women at cardiovascular risk.

BACKGROUND: Cardiovascular disease is the primary cause of death in women. Prevention, screening and diagnosis are generally implemented at later stages and less frequently than in men, and provision of treatment is not optimal in women. AIMS: To assess the relevance of targeted screening for myocardial ischaemia in women with multiple risk factors, and to identify which specific factors target women more effectively. METHODS: We undertook a prospective observational study with retrospective data collection based on a cohort of symptomatic or asymptomatic women with multiple cardiovascular risk factors. All women underwent non-invasive diagnostic testing through the "Heart, arteries and women", healthcare pathway available at Lille University Hospital, between 1 January 2013 and 30 June 2014. RESULTS: Screening was positive in 15.7% of the 287 participants. Thirty women had a coronary angiography: of these, 22 (73.3%) had no evidence of obstructive coronary artery disease. The independent predictive factors for positive screening were >5 years since menopause (odds ratio [OR] 3.9; P=0.0016); high-density lipoprotein cholesterol ≤0.5g/dL (OR 2.3; P=0.0356); and body mass index ≥30kg/m2 (OR 3.7; P=0.0009). Symptoms were predictive of positive screening (P=0.010), but were mostly atypical. Based on these observations, we developed a clinical coronary score to target screening more efficiently (area under the curve 0.733). Positive screening resulted in low rates of revascularization (16.6%), but a significant increase in the prescription of statins (P=0.002), antiplatelet agents (P<0.0001) and beta-blockers (P=0.024). CONCLUSION: Screening for myocardial ischaemia among selected women at risk of cardiovascular disease can be useful to improve medical treatment.

Cardiopulmonary exercise testing is a better outcome predictor than exercise echocardiography in asymptomatic aortic stenosis.

BACKGROUND: Objective assessment of maximal aerobic capacity using peak oxygen consumption (peak VO2) can be helpful in the management of patients with asymptomatic aortic stenosis (AS). The relationship between peak VO2 and AS severity criteria derived from rest and supine exercise echocardiography (SEE) has never been explored. OBJECTIVES: We aimed to determine whether low peak VO2 (<85% of predicted value) is associated with severity parameters in SEE, and poor clinical outcome. METHODS: Fifty one asymptomatic patients (mean age of 54±21years) with moderate to severe aortic stenosis (Vmax>3m/s) and left ventricle ejection fraction>50% prospectively underwent resting and SEE and cardiopulmonary exercise testing (CPX). RESULTS: Peak VO2 was lower than expected (21.9±7.4mL/kg/min), i.e. <85% of predicted value in 57% patients, secondary to cardiac limitation in most of them (69%). In multiple regression analysis, age, BMI and female gender were the only independent determinants of peak VO2. Interestingly no parameter derived from SEE was associated with peak VO2. After 21±7month follow-up, no patient died, 20 underwent cardiac surgery. Peak VO2<85% of predicted value was associated with lower event free survival compared to normal peak VO2 (57%±11% vs 93±6%, p=0.036) whereas no exercise echocardiographic parameter could predict such events. Peak VO2≥85% had a negative predictive value of 97%. CONCLUSION: CPX detects a high proportion of false asymptomatic AS patients with poorer outcome that cannot be predicted by SEE markers of AS severity. Assessment of aerobic capacity should be part of current approach within a "watchful waiting" strategy.

To spare or not to spare ? The aortic valve in scleroderma and aortic root aneurysm.

Acute valve-sparing procedures are effective in the treatment of aortic root dilation when there is no valve pathology. In this review, we discuss the role of aortic valve-sparing procedures in the presence of connective tissue disorders such as scleroderma.

Right ventricular systolic function in organic mitral regurgitation: impact of biventricular impairment.

BACKGROUND: To assess the prevalence, determinants, and prognosis value of right ventricular (RV) ejection fraction (EF) impairment in organic mitral regurgitation. METHODS AND RESULTS: Two hundred eight patients (62±12 years, 138 males) with chronic organic mitral regurgitation referred to surgery underwent an echocardiography and biventricular radionuclide angiography with regional function assessment. Mean RV EF was 40.4±10.2%, ranging from 10% to 65%. RV EF was severely impaired (≤35%) in 63 patients (30%), and biventricular impairment (left ventricular EF<60% and RV EF≤35%) was found in 34 patients (16%). Pathophysiologic correlates of RV EF were left ventricular septal function (ß=0.42, P<0.0001), left ventricular end-diastolic diameter index (ß=-0.22, P=0.002), and pulmonary artery systolic pressure (ß=-0.14, P=0.047). Mitral effective regurgitant orifice size (n=84) influenced RV EF (ß=-0.28, P=0.012). In 68 patients examined after surgery, RV EF increased strongly (27.5±4.3-37.9±7.3, P<0.0001) in patients with depressed RV EF, whereas it did not change in others (P=0.91). RV EF ≤35% impaired 10-year cardiovascular survival (71.6±8.4% versus 89.8±3.7%, P=0.037). Biventricular impairment dramatically reduced 10-year cardiovascular survival (51.9±15.3% versus 90.3±3.2%, P<0.0001; hazard ratio, 5.2; P<0.0001) even after adjustment for known predictors (hazard ratio, 4.6; P=0.004). Biventricular impairment reduced also 10-year overall survival (34.8±13.0% versus 72.6±4.5%, P=0.003; hazard ratio, 2.5; P=0.005) even after adjustment for known predictors (P=0.048). CONCLUSIONS: In patients with organic mitral regurgitation referred to surgery, RV function impairment is frequent (30%) and depends weakly on pulmonary artery systolic pressure but mainly on left ventricular remodeling and septal function. RV function is a predictor of postoperative cardiovascular survival, whereas biventricular impairment is a powerful predictor of both cardiovascular and overall survival.

Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial.

AIMS: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. METHODS AND RESULTS: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. CONCLUSION: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

Echocardiography predictors and prognostic value of pulmonary artery systolic pressure in chronic organic mitral regurgitation.

OBJECTIVE: To evaluate the predictors of pulmonary artery systolic pressure (PASP) in organic mitral regurgitation (MR) and its prognostic value after surgery. DESIGN: Prospective observational study, conducted from 1998 to 2006. SETTING: Echocardiography and cardiac surgery departments, University Hospital. PATIENTS: Echocardiography was carried out in 256 patients (63+/-12 years, 170 male) with organic MR (degenerative aetiology: 91%) referred for surgery. MAIN OUTCOME MEASURES: Echocardiography predictors of PASP. Postoperative end points were overall mortality and cardiovascular mortality. RESULTS: Baseline PASP was 45+/-14 mmHg, ranging from 25 to 105 mmHg. PASP was > or = 50 mmHg in 82 patients (32%). Left atrial volume (p=0.003), mitral deceleration time (p<0.0001) and mitral medial E/E' (p<0.0001) were independent predictors of PASP, whereas left ventricular size and systolic function were not predictors. Mitral valve repair was performed in 194 patients (76%) and mitral valve replacement in 62 (24%). In a Cox model mitral valve repair (HR=0.41 (95% CI 0.20 to 0.85), p=0.016) and PASP (HR=1.43 (95% CI 1.09 to 1.88) per 10 mmHg increment, p=0.011) were independent predictors of overall mortality, even after adjustment for known predictors. PASP (HR=1.49 (95% CI 1.03 to 2.16) per 10 mmHg increment, p=0.033) was also an independent predictor of cardiac mortality. Eight-year survival after surgery was 58.6% and 86.6% in patients with baseline PASP > or = 50 mmHg or <50 mmHg, respectively (p<0.0001). CONCLUSIONS: In organic MR, mitral deceleration time, mitral E/E' and left atrial volume correlate with PASP. Pulmonary artery systolic pressure > or = 50 mmHg is an independent predictor of overall and cardiovascular mortality after surgery in organic MR.

High-resolution melting analysis of sequence variations in the cytidine deaminase gene (CDA) in patients with cancer treated with gemcitabine.

Gemcitabine (2',2'-difluorodeoxycytidine) is a major antimetabolite cytotoxic drug with a wide spectrum of activity against solid tumors. Hepatic elimination of gemcitabine depends on a catabolic pathway through a deamination step driven by the enzyme cytidine deaminase (CDA). Severe hematologic toxicity to gemcitabine was reported in patients harboring genetic polymorphisms in CDA gene. High-resolution melting (HRM) analysis of polymerase chain reaction amplicon emerges today as a powerful technique for both genotyping and gene scanning strategies. In this study, 46 DNA samples from gemcitabine-treated patients were subjected to HRM analysis on a LightCycler 480 platform. Residual serum CDA activity was assayed as a surrogate marker for the overall functionality of this enzyme. Genotyping of three well-described single nucleotide polymorphisms in coding region (c.79A>C, c.208G>A and c.435C>T) was successfully achieved by HRM analysis of small polymerase chain reaction fragments, whereas unknown single nucleotide polymorphisms were searched by a gene scanning strategy with longer amplicons (up to 622 bp). The gene scanning strategy allowed us to find a new intronic mutation c.246+37G>A in a female patient displaying marked CDA deficiency and who had an extreme toxic reaction with a fatal outcome to gemcitabine treatment. Our work demonstrates that HRM-based methods, owing to their simplicity, reliability, and speed, are useful tools for diagnosis of CDA deficiency and could be of interest for personalized medicine.

Prospective assessment of multiple cardiac papillary fibroelastomas: an echocardiographic and surgical study.

Multiple cardiac papillary fibroelastomas (PFEs) are thought to account for less than 10% of patients with PFE. We aimed at evaluating the frequency and location of multiple PFEs and the reliability of transthoracic (TTE) and transoesophageal (TEE) echocardiography in diagnosing multiple PFEs. Twenty-six consecutive patients (52±14 years, 65% males) with pathologically confirmed PFE had 21 PFEs diagnosed by TTE, 33 by TEE, and 62 at surgery. Eight patients (31%) had multiple PFEs found either by TEE or at surgery. Aortic valve was involved in 75% of patients with multiple PFEs and left ventricle in 38% of patients. The sensitivity of TTE in diagnosing any PFEs was 51.3% and 76.9% for TEE. Our study emphasizes the high frequency of multiple PFEs, the need of TEE for all presumed PFE and the need for careful assessment of left-sided endocardial surfaces, especially of the aortic valve, during PFE excision.

Clinical value of exercise Doppler echocardiography in patients with cardiac-valvular disease.

Besides its usefulness for the detection of exercise-induced ischemia, conventional exercise testing may help to predict the onset of clinical events and the need for surgery in asymptomatic patients with cardiac-valvular disease. Doppler echocardiography examination during exercise recently emerged as a new stress testing modality that may add useful information regarding dynamism of LV function, valve disease severity and pulmonary circulation. Few studies have demonstrated a correlation between the results of exercise Doppler echocardiography and clinical outcome. Preliminary experience needs to be confirmed to warrant routine use of Doppler echocardiography examination during exercise in the evaluation of patients with cardiac-valve disease.

Conservative surgical treatment for active infective tricuspid valve endocarditis according to the "clover technique".

AIMS: This prospective study was undertaken to analyze the outcomes of conservative surgery with the "clover technique" for active infective tricuspid valve endocarditis. METHODS: Five consecutive patients underwent surgery for active infective tricuspid valve endocarditis. The mean age was 36.6 years. Four of the patients were men. In all patients, the tricuspid valve had become mutilated and infected. One patient had associated mitral endocarditis, and one had aortic endocarditis. Staphylococcus aureus was the most common bacterial species. Conservative surgery was indicated in all patients with infection limited to the leaflets and/or subvalvular apparatus of the tricuspid valve. Total resection of infected tissues was achieved in all cases. The tricuspid valve was then reconstructed according to the clover technique. A tricuspid annular ring was used in 2 patients. RESULTS: All 5 patients survived surgery. Intraoperative transesophageal and predischarge transthoracic echocardiographic evaluations showed good results in all patients. The mean follow-up time was 26.4 +/- 12.5 months. No recurrent bacterial tricuspid endocarditis occurred during follow-up. All patients were in New York Heart Association functional class I. A transthoracic echocardiography evaluation at the latest control examination showed trivial leakage (3 patients) or no residual regurgitation (2 patients); no transvalvular gradient was found in any of the patients. No tricuspid valve calcification has been detected to date. Cardiac magnetic resonance imaging analyses showed no postoperative void flow and confirmed the preservation of right ventricular function and thus the reliability of this technique. CONCLUSIONS: This novel technique is indicated for tricuspid valve endocarditis and should be considered as an adequate approach in cases of uncontrollable infection involving the tricuspid valve that is responsible for extended valve destruction.

Assessment of papillary fibroelastomas with live three-dimensional transthoracic echocardiography.

Seven consecutive patients presenting with typical echocardiographic features of papillary fibroelastoma requiring surgery were studied. All patients underwent standard two-dimensional (2D) transthoracic echocardiography (TTE) followed by live three-dimensional (live 3D) echocardiography with data set storage allowing analysis with systematic cropping of the acquired 3D data and volume measurement of the lesions. Assessment of papillary fibroelastoma by 2D and live 3D TTE was compared to operative findings. The feasibility of live 3D echocardiography in this setting was 100%. The quality of images was considered as optimal in three patients, good in three patients, and poor in one patient. A typical speckled appearance of the tumor was observed in three patients presenting with large tumors. The location of the tumor attachment was precisely defined in all but one patient, with a clear improvement in spatial assessment with live 3D TTE in three patients. Live 3D TTE also improved the operative planning in three patients. Live 3D TTE appears to be useful in the assessment of intracardiac tumors as small as papillary fibroelastomas, leading to a comprehensive approach of the lesion and facilitating the operative planning.

Cardiovascular risk factors as predictors of early and late survival after bioprosthetic valve replacement for aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Cardiovascular risk factors have been associated with aortic valve stenosis, which is considered as an atherosclerosis-like process. The study aim was to assess the effect of cardiovascular risk factors on early and late outcome after valve replacement with a bioprosthesis for aortic stenosis (AS), and the impact of these factors on the outcome of the bioprosthesis. METHODS: Preoperative clinical, biological and echocardiographic data were recorded in 222 patients (110 males, 112 females; mean age 73 +/- 8 years) who underwent surgery for severe AS between 1989 and 1993. The mean follow up was 7.3 +/- 4.7 years; total follow up was 1,621 patient-years (pt-yr). RESULTS: Overall 12-year actuarial survival rate was 36.1%. Independent predictors of mortality were age (hazards ratio (HR) 1.11; 95% CI: 1.08-1.14, p < 0.0001), diabetes mellitus (DM) (HR 2.53; 95% CI: 1.65-3.88, p < 0.0001), male gender (HR 2.17; 95% CI: 1.53-3.12, p < 0.0001), and NYHA class (HR 1.66; 95% CI: 1.17-2.34, p = 0.004). Other cardiovascular risk factors had no significant effect on survival. DM and NYHA class were also independent predictive factors for valve-related death and overall valve-related complications. The 12-year actuarial survival was 13% in DM patients compared to 38% in non-diabetic patients (p = 0.003), with a significant increase in cardiovascular death (p = 0.0028), and a non-significant increase in thromboembolic events (p = 0.08) in DM patients. The only independent predictive risk factor of structural valve failure in multivariate analysis was renal failure (HR 1.1, 95% CI: 1.03-1.16, p = 0.047). Cardiovascular risk factors such as hypercholesterolemia, DM, hypertension, tobacco smoking and obesity had no effect on the outcome of the bioprosthesis. CONCLUSION: Age, male gender, DM and NYHA class were the main predictors for long-term mortality after bioprosthesis implantation for AS. DM significantly impaired survival, with an excess of cardiovascular deaths and thromboembolic events. Other cardiovascular risk factors had no significant effect on either survival or bioprosthesis durability.